Amphotropic mouse retroviruses will be engineered to serve as vectors for introducing genes into hematopoietic stem cells more efficiently. Studies will be carried out with mouse and human bone marrow. Conditions for optimizing infectivity of viruses will be studied by using "crippled" strains containing inserted neomycin-resistance gene and glucocerebrosidase cDNA. Expression of human glucocerebrosidase in mouse hematopoietic stem cells will be demonstrated with mouse-mouse monoclonal antibodies. In the case of human cells, attempts will be made to demonstrate expression of the gene by both immunologic and activity measurements, using cultured fibroblasts and bone marrow stem cells from patients with Gaucher disease as a target. The reagents developed in these investigations, the DNA probes and antibodies, will be used to determine whether messenger RNA is formed in Gaucher disease cells, to study the possible linkage of various types of Gaucher genes to restriction polymorphisms, to investigate whether processing of glucocerebrosidase occurs and whether such processing is helpful in distinguishing different types of Gaucher disease. cDNA from patients with the different types of Gaucher disease will be sequenced to determine whether specific portions of the molecule are involved in specific disease types and to provide better understanding of the degree of diversity of Gaucher's disease within the Jewish population.